Philanjalo CDC Grant Application, FOA CDC-RFA-GH-11-005 Project Abstract Improving Isoniazid Preventive Therapy Penetration among HIV infected Individuals through Intensification of Case Finding at the Community Level in Rural South Africa South Africa's raging HIV epidemic has resulted in tuberculosis (TB) rates that are nearly three hundred times the levels in the United States. South Africa has the largest global burden of HIV/TB coinfection and among the highest rates of drug resistant TB, with consequent high rates of morbidity and mortality that have severe consequences for TB control and antiretroviral therapy roll out programs. The World Health Organization has promoted the 3Is for TB control: 1) intensive case finding (ICF), 2) infection control and 3) isoniazid preventive therapy (IPT), and has strongly recommended implementation of IPT for HIV positive individuals with latent TB infection (LTBI) as part of a comprehensive package of services to control TB. The uptake of IPT to date has been poor and new strategies with careful evaluation are critically needed. ICF programs can increase active TB case detection and when integrated with HIV case finding can also potentially detect out of care HIV positive patients eligible for IPT and thereby increase IPT uptake. This integrated strategy of IPT nested within a community based ICF program combines 2 of the 3 I's in an innovative manner, has not been studied, and holds promise of reducing TB morbidity and mortality and decreasing TB transmission, among HIV infected individuals. We propose such a model strategy of IPT, nested into a larger community based HIV and TB intensive case finding (ICF) program developed and being implemented and evaluated by Philanjalo and Yale University in a rural, resource limited setting with among the highest rates of TB and HIV in the world. This operational research proposal aims to demonstrate the feasibility of integrating and to provide new knowledge regarding two innovative TB control strategies to identify eligible HIV infected individuals for IPT, link these patients to clinical care, and facilitate successful both TB preventive therapy and HIV care and treatment. The effectiveness of these linked community-based ICF and IPT strategies will be measured by the following primary outcomes: 1) uptake of IPT among HIV+ individuals diagnosed through the ICF model 2) initiation, adherence and completion of a 6 month IPT regimen 3) entry into and monitoring of HIV care 4) determine the cost effectiveness of such a strategy and 5) provide empiric data to enable mathematical modeling of the strategy's impact on the study population and beyond. This project is of great public health importance and will be conducted by Philanjalo, in collaboration with the South African KwaZulu Natal provincial Department of Health, and Yale University.